Methods and compositions for determining responsiveness to antibody therapy

Abstract

Methods and compositions are provided for determining whether a subject suffering from a neoplastic condition is responsive to an antineoplastic therapy, such as antibody therapy, e.g., Rituximab. In practicing the subject methods, the subject is genotyped to determine whether the subject has a least one favorable FcγR polymorphism, e.g., the 131 H/H genotype or the 158 V/V genotype. In addition, reagents, devices and kits thereof, that find use in practicing the subject methods are provided.

1 - 43 . (canceled) 
     
     
         44 . A method of predicting whether a subject suffering from a neoplastic disease will respond to an antineoplastic therapy, said method comprising:
 (a) determining in said subject at least an FcγRIIa polymorphism; and   (b) employing said determination to predict the relative responsiveness of said subject to said antineoplastic therapy.   
     
     
         45 . The method according to  claim 44 , wherein said FcγRIIa polymorphism is the 131 H/R polymorphism. 
     
     
         46 . The method according to  claim 45 , wherein identification of the 131 H/H polymorphism indicates higher relative responsiveness to said antineoplastic therapy compared to the 131 R containing polymorphism. 
     
     
         47 . The method according to  claim 44 , wherein said method further comprises determining in said subject an FcγRIIIa polymorphism. 
     
     
         48 . The method according to  claim 47 , wherein said FcγRIIIa polymorphism is the 158 V/F polymorphism. 
     
     
         49 . The method according to  claim 48 , wherein identification of the FcγRIIa 131 H/H polymorphism and/or the FcγRIIIa 158 V/V polymorphism indicates higher relative responsiveness to said antineoplastic therapy compared to those polymorphisms lacking both the FcγRIIa 131 H/H and FcγRIIIa 158 V/V polymorphisms. 
     
     
         50 . The method of  claim 44 , wherein said prediction contributes to a decision on how or whether to treat said subject. 
     
     
         51 . The method according to  claim 44 , wherein:
 a) said neoplastic disease is:
 i) non-Hodgkin's lymphoma (NHL); or 
 ii) said NHL is follicular lymphoma; or 
   b) said antibody therapy comprises:
 i) use of a therapeutic antibody or mimetic thereof that specifically binds to CD20; 
 ii) a monoclonal antibody therapy; or 
 iii) a monoclonal antibody which is rituximab therapy. 
   
     
     
         52 . A method of evaluating a patient having a neoplastic condition, wherein said evaluation includes determination of an FcγRIIa 131 polymorphism of said patient, and said determination is a component of treatment decision for said patient. 
     
     
         53 . The method of  claim 52 , wherein said method further includes determination of an FcγRIIIa polymorphism 158 of said patient. 
     
     
         54 . The method of  claim 53 , wherein said treatment decision includes: (a) deciding a treatment strategy based on the evaluation, (b) a decision to not treat, (c) a decision to initiate treatment, or (d) a decision to treat, including with an antibody therapy. 
     
     
         55 . The method of  claim 54 , wherein said method further includes a treatment step. 
     
     
         56 . The method of  claim 52 , wherein an FcγRIIa 131 polymorphism is H/H, which has a different responsiveness from an FcγRIIa 131 polymorphism which is R containing. 
     
     
         57 . The method of  claim 53 , wherein the FcγRIIa and FcγRIIIa polymorphisms within the group of 131 H/H and/or 158 V/V has a different responsiveness to treatment with monoclonal antibody from the group whose polymorphisms lack both 131 H/H and 158 V/V. 
     
     
         58 . The method of  claim 54 , wherein:
 a) said neoplastic condition is:
 i) non-Hodgkin's lymphoma (NHL); or 
 ii) said NHL is follicular lymphoma; or 
   b) said treatment decision is treatment with:
 i) antibody therapy; 
 ii) antibody therapy which comprises use of a therapeutic antibody or mimetic thereof that specifically binds to CD20; 
 iii) antibody therapy which is a monoclonal antibody therapy; or 
 iv) antibody therapy which comprises rituximab therapy. 
   
     
     
         59 . A method of selecting a group of patients exhibiting symptoms of a neoplastic disease predicted to have similar responsiveness to antibody therapy, said method comprising:
 (a) evaluating said patients for both FcγRIIa 131 and FcγRIIIa 158 polymorphisms according to the method of  claim 53 , and   (b) selecting a group having polymorphisms with similar responsiveness.   
     
     
         60 . The method of  claim 59 , wherein said group includes one or more of:
 a) both FcγRIIa 131 H/H and FcγRIIIa V/V containing polymorphisms; or   b) neither FcγRIIa 131 H/H nor FcγRIIIa V/V containing polymorphisms.   
     
     
         61 . A kit or device for evaluating the polymorphisms of a biosample from a patient comprising a neoplastic condition, said kit or device comprising an element to evaluate the FcγRIIa 131 polymorphism, including 131 H/R polymorphism, of said biosample. 
     
     
         62 . The kit or device of  claim 61 , wherein said element allows evaluation of a nucleic acid or protein in said biosample. 
     
     
         63 . The kit or device of  claim 61 , wherein said kit or device further allows evaluation of an FcγRIIIa 158 polymorphism, including 158 V/F polymorphism.